Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers
Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers
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DOI：
10.1002/glia.20503
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发表时间：
2007-05-01
期刊：
影响因子：
6.2
通讯作者：
Yuki, Nobuhiro
中科院分区：
文献类型：
--
作者：
Susuki, Keiichiro;Baba, Hiroko;Yuki, Nobuhiro
旁结轴-胶质连接对于有髓神经纤维中的离子通道聚集和快速动作电位传播是重要的。旁阳极的形成依赖于神经胶质细胞中的细胞粘附分子神经成束蛋白（NF）155，以及轴突中的Caspr和contactin异源二聚体。我们发现神经节苷脂GM 1抗体标记结旁区。神经节苷脂GM 1和GD 1a的自身抗体被认为破坏外周运动神经中的朗维尔结并引起格林-巴利综合征，这是一种以急性肢体无力为特征的自身免疫性神经病。为了阐明神经节苷脂在郎维尔结及其附近的功能，我们检查了缺乏神经节苷脂（包括GM 1和GD 1a）的小鼠的节点。在外周和中枢神经系统中，一些结旁环未能附着到轴膜，并且Caspr和NF 155的免疫染色减弱。K+通道在腹肢节被错误定位到副阳极，节Na+通道簇被加宽。随着年龄的增长，副阳极的异常免疫染色变得更加突出。此外，这种缺陷在腹根比背根更普遍，在缺乏b系列神经节苷脂但GM 1和GD 1a过量的突变小鼠中不太常见。电生理研究显示，神经传导减慢和减少节点Na+电流突变的外周运动神经。在低密度，洗涤剂不溶性膜级分中的Caspr和NF 155的量在突变体脑中减少。这些结果表明，神经节苷脂是脂筏成分，有助于稳定和维持神经元-胶质细胞的相互作用在paranodes。(c)2007 Wiley-Liss，Inc.
Paranodal axo-glial junctions are important for ion channel clustering and rapid action potential propagation in myelinated nerve fibers. Paranode formation depends on the cell adhesion molecules neurofascin (NF) 155 in glia, and a Caspr and contactin heterodimer in axons. We found that antibody to ganglioside GM1 labels paranodal regions. Autoantibodies to the gangliosides GM1 and GD1a are thought to disrupt nodes of Ranvier in peripheral motor nerves and cause Guillain-Barre syndrome, an autoimmune neuropathy characterized by acute limb weakness. To elucidate ganglioside function at and near nodes of Ranvier, we examined nodes in mice lacking gangliosides including GM1 and GD1a. In both peripheral and central nervous systems, some paranodal loops failed to attach to the axo-lemma, and immunostaining of Caspr and NF155 was attenuated. K+ channels at juxtaparanodes were mislocalized to paranodes, and nodal Na+ channel clusters were broadened. Abnormal immunostaining at paranodes became more prominent with age. Moreover, the defects were more prevalent in ventral than dorsal roots, and less frequent in mutant mice lacking the b-series gangliosides but with excess GM1 and GD1a. Electrophysiological studies revealed nerve conduction slowing and reduced nodal Na+ current in mutant peripheral motor nerves. The amounts of Caspr and NF155 in low density, detergent insoluble membrane fractions were reduced in mutant brains. These results indicate that gangliosides are lipid raft components that contribute to stability and maintenance of neuron-glia interactions at paranodes. (c) 2007 Wiley-Liss, Inc.